Frequent loss of sequences from the long arm of chromosome 10 in endometrial cancers
- Washington Univ. St. Louis, MO (United States); and others
Endometrial cancer is the most common gynecological malignancy in the United States, with an estimated 33,000 new cases diagnosed annually. Cancers develop as the result of the accumulation of mutations in proto-oncogenes and tumor suppressor genes. Mutations in KRAS and TP53 in endometrial cancer have been reported, but for the most part the genetic events underlying endometrial tumorigenesis have not been defined. Previous loss of heterozygosity studies (LOH) in endometrial cancers revealed frequent loss of sequences from 3p, 10q, 17p and 18q, suggesting a role for tumor suppressor genes that lie within these regions of loss. We have undertaken a series of experiments to identify tumor suppressor genes involved in endometrial tumorigenesis, focusing on a region of chromosome 10 that is likely to include a novel tumor suppressor gene. We have allelotyped 40 normal/tumor DNA pairs with 5 microsatellite repeat markers from 10q and one from 10p. LOH for at least one 10q marker was seen in 45% of informative samples. Chromosome 10 LOH was seen most frequently in Grade 1 adenocarcinoma (5/8; 60%). Grade 3 adenocarcinomas were also characterized by LOH of 10q sequences. Grade 2 tumors, on the other hand, did not reveal chromosome 10 LOH but were instead characterized by frequent microsatellite instability (RER). Other tumor types did not show the same patterns of genetic alteration seen in adenocarcinoma. We are currently defining the smallest region(s) of loss on 10q by typing 75 tumor/normal pairs using a set of ordered microsatellite repeat markers from distal 10q. A candidate tumorigenesis gene within what is the common region of deletion is being characterized in detail in a series of tumors.
- OSTI ID:
- 133554
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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